Evidence map›Paper›PMID 30778524›Full record

ArticleCardiovascular research2019

Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency.

Kim L Ho, Liyan Zhang, Cory Wagg, Rami Al Batran, Keshav Gopal, Jody Levasseur, Teresa Leone, Jason R B Dyck, John R Ussher, Deborah M Muoio and 2 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06398964 (Effects of 2-week Ketosis on Myocardial Ketone Body Consumption, Utilization, and External Efficiency in Patients With Chronic Heart Failure), which is not on this map. Cited by 128 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 2 pooled it
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06398964 nacompletednot on this mapstarted 2023, after this paper: background citation

Effects of 2-week Ketosis on Myocardial Ketone Body Consumption, Utilization, and External Efficiency in Patients With Chronic Heart Failure

TypeinterventionalSponsorAarhus University HospitalRan2023 to 2025Enrolled12ConditionsHeart Failure With Reduced Ejection FractionArms3-hydroxybutyrat, Isocaloric placebo drink
3 · Its place in the literature

Who cites it

128 citing papers in PubMed, 2 syntheses or guidelines pooled it, 188 citations in OpenAlex.

  1. Pooled it
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  4. Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2023
    Trial
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  14. Sarco/Endoplasmic Reticulum CaJournal of the American Heart Association · 2026
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68 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Kim L HoCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Liyan ZhangCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Cory WaggCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Rami Al BatranCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Keshav GopalCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Jody LevasseurCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Teresa LeonePenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, USA.
Jason R B DyckCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
John R UssherCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
Deborah M MuoioDuke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, 300 N Duke St, Durham, NC, USA.
Daniel P KellyPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, USA.
Gary D LopaschukCardiovascular Research Centre, Faculty of Medicine and Dentistry, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada.
University of Alberta · CAUniversity of Pennsylvania · US

Funding

Probing the Role of Mitochondrial Short-chain Carbon Homeostasis in the Hypertrophied and Failing HeartR01HL128349 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUOIO, DEBORAH M · 2016 to 2024
$6.1M
NHLBI NIH HHS R01 HL128349
6 · The paper itself

Abstract

aimsThe failing heart is energy-starved and inefficient due to perturbations in energy metabolism. Although ketone oxidation has been shown recently to increase in the failing heart, it remains unknown whether this improves cardiac energy production or efficiency. We therefore assessed cardiac metabolism in failing hearts and determined whether increasing ketone oxidation improves cardiac energy production and efficiency. METHODS AND

resultsC57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery to induce pressure overload hypertrophy over 4-weeks. Isolated working hearts from these mice were perfused with radiolabelled β-hydroxybutyrate (βOHB), glucose, or palmitate to assess cardiac metabolism. Ejection fraction decreased by 45% in TAC mice. Failing hearts had decreased glucose oxidation while palmitate oxidation remained unchanged, resulting in a 35% decrease in energy production. Increasing βOHB levels from 0.2 to 0.6 mM increased ketone oxidation rates from 251 ± 24 to 834 ± 116 nmol·g dry wt-1 · min-1 in TAC hearts, rates which were significantly increased compared to sham hearts and occurred without decreasing glycolysis, glucose, or palmitate oxidation rates. Therefore, the contribution of ketones to energy production in TAC hearts increased to 18% and total energy production increased by 23%. Interestingly, glucose oxidation, in parallel with total ATP production, was also significantly upregulated in hearts upon increasing βOHB levels. However, while overall energy production increased, cardiac efficiency was not improved.

conclusionsIncreasing ketone oxidation rates in failing hearts increases overall energy production without compromising glucose or fatty acid metabolism, albeit without increasing cardiac efficiency.

Indexed as

Energy MetabolismVentricular Function, Left3-Hydroxybutyric AcidAcetylationAcyl-CoA Dehydrogenase, Long-ChainAdaptation, PhysiologicalAnimalsDisease Models, AnimalFatty AcidsGlucoseHeart FailureHypertrophy, Left VentricularMaleMice, Inbred C57BLMyocardiumOxidation-Reduction3-Hydroxybutyric AcidAcyl-CoA Dehydrogenase, Long-ChainFatty AcidsGlucoseBeta-hydroxybutyrateCardiac Energy metabolismHeart failureHypertrophyKetone body oxidation

Identifiers

PMID30778524
PMCPMC6704391
OpenAlexW2917226475

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.